Læknablaðið : fylgirit - 01.05.1978, Page 64

PLASMA
NAPROXEN
pg/ml
PLASMA NAPROXEN •----•
PLASMA DES-METHYL-NAPROXEN O—-O
(jg/ml
2 4 6 8 10
HOURS AFTER INGESTION
Fig. 2 The biological half timc of naproxen,
calculated from the 4 hour and the 8
hour values in three uremic patients
after 250 mg of naproxen (single dose).
Fig. 1 Plasma levels of naproxen and 6-des-
methyl naproxen in patient R.O. after
250 mg of naproxen as a single dose.
was 26 ug/ml 12 hours after dose end 44 ug/ml
6 hours after dose. The expected values (2)
should have been higher, 40 ug/ml and 55 ug/ml
respectively.
Results in patient M.J. (one sample lost and
a last sample drawn 24 hours after last dose)
is shown separately in Table II. High values of
6-des-methyl naproxen are still present 24
hours after the last dose of napraxen.
Side effects. No side effects were
experienced by those four uremic patients
obtaining napraxen 250 mg x 2 for 5-8 days.
One of the patients who had osteo-arthritic
symptoms claimed to have been improved.
Discussion:
The presented pilot study, though dealing with
only a small number of uremic subjects, seems
to permit the conclusion that naproxen itself is
not accumulated in plasma in patients with renal
failure although its main metaboiite, 6-des-
methyl naproxen is accumulated in such patients.
In fact surprisingly low plasma values of
naproxen was found in patients with renal
insufficiency. As shown in Fig. 2 this could be
due to a shorter biological half-time for the
drug in uremia. However, as shown in Table
m, other drugs were given to the investigated
patients; drugs not unlikely to have disturbed
the gastrointestinal absorption of naproxen
(aluminiumhydroxide), interfered with its binding
to plasma protein (dicumarol, digoxin, dicloxa-
cillin) or to have disturbed the chromatographic
analysis. The reversed liquid chromatography
method used in the present study is still under
development and the analysis of samples from
uremic patients offered some difficulties not
encountered in healthy subjects, particularly as
regards the determination of 6-des-methyI
naproxen. It remains to determine to which
extent these problems were due to retained
substances connected with uremia per se or
62